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心血管健康与疾病中的氧化还原信号传导及氧化还原生物标志物

Redox-signalling and Redox Biomarkers in Cardiovascular Health and Disease.

作者信息

Sultana Yasmin, Kaur Lang Damanpreet, Santosh Alex Thomson, Khabiya Rakhi, Dwivedi Akanksha, Sen Saikat, Chakraborty Raja

机构信息

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India.

Chitkara College of Pharmacy, Chitkara University, Punjab, India.

出版信息

Cardiovasc Hematol Agents Med Chem. 2024 Feb 15. doi: 10.2174/0118715257282030240130095754.

Abstract

Overproduction of reactive nitrogen and oxygen species (RNS and ROS) has been linked to the pathogenesis of diabetes, hypertension, hyperlipidemia, stroke, angina, and other cardiovascular diseases. These species are produced in part by the mitochondrial respiratory chain, NADPH oxidase, and xanthine oxidase. RNS and ROS both contribute to oxidative stress, which is necessary for the development of cardiovascular disorders. In addition to ROS species like hydroxyl ion, hydrogen peroxide, and superoxide anion, RNS species like nitric oxide, peroxynitrous acid, peroxynitrite, and nitrogen dioxide radicals have also been linked to a number of cardiovascular conditions. They promote endothelial dysfunction, vascular inflammation, lipid peroxidation, and oxidative damage, all of which contribute to the development of cardiovascular pathologies. It's crucial to understand the mechanisms that result in the production of RNS and ROS in order to identify potential therapeutic targets. Redox biomarkers serve as indicators of oxidative stress, making them crucial tools for diagnosing and predicting cardiovascular states. The advancements in proteomics, metabolomics, genomics, and transcriptomics have made the identification and detection of these small molecules possible. The following redox biomarkers are notable examples: 3-nitrotyrosine, 4-hydroxy-2-nonenal, 8- iso-prostaglandin F2, 8-hydroxy-2-deoxyguanosine, malondialdehyde, Diacron reactive oxygen metabolites, total thiol, and specific microRNAs (e.g. miRNA199, miRNA21, miRNA1254, miRNA1306-5p, miRNA26b-5p, and miRNA660-5p) are examples. Although redox biomarkers have great potential, their clinical applicability faces challenges. Redox biomarkers frequently have a short half-life and exist in small quantities in the blood, making them challenging to identify and measure. The interpretation of biomarker data may also be influenced by confounding factors and the complex interplay of various oxidative stress pathways. Therefore, in-depth validation studies and the development of sensitive and precise detection methods are needed to address these problems. In the search for redox biomarkers, cutting-edge techniques like mass spectrometry, immunoassays, and molecular diagnostics are applied. New platforms and technologies have made it possible to accurately detect and monitor redox biomarkers, which facilitates their use in clinical settings. Our expanding knowledge of RNS and ROS involvement in cardiovascular disorders has made it possible to develop redox biomarkers as diagnostic and prognostic tools. Overcoming the challenges associated with their utility and utilizing advanced detection techniques, which will improve their clinical applicability, will ultimately benefit the management and treatment of cardiovascular conditions.

摘要

活性氮和氧物种(RNS和ROS)的过量产生与糖尿病、高血压、高脂血症、中风、心绞痛及其他心血管疾病的发病机制有关。这些物种部分由线粒体呼吸链、NADPH氧化酶和黄嘌呤氧化酶产生。RNS和ROS都促成氧化应激,而氧化应激是心血管疾病发展所必需的。除了如氢氧根离子、过氧化氢和超氧阴离子等ROS物种外,一氧化氮、过氧亚硝酸、过氧亚硝酸盐和二氧化氮自由基等RNS物种也与多种心血管疾病有关。它们会促进内皮功能障碍、血管炎症、脂质过氧化和氧化损伤,所有这些都促成心血管疾病的发展。了解导致RNS和ROS产生的机制对于确定潜在的治疗靶点至关重要。氧化还原生物标志物作为氧化应激的指标,是诊断和预测心血管状态的关键工具。蛋白质组学、代谢组学、基因组学和转录组学的进展使得识别和检测这些小分子成为可能。以下是一些值得注意的氧化还原生物标志物示例:3 - 硝基酪氨酸、4 - 羟基 - 2 - 壬烯醛、8 - 异前列腺素F2、8 - 羟基 - 2 - 脱氧鸟苷、丙二醛、戴克隆活性氧代谢物、总硫醇以及特定的微小RNA(如miRNA199、miRNA21、miRNA1254、miRNA1306 - 5p、miRNA26b - 5p和miRNA660 - 5p)。尽管氧化还原生物标志物具有巨大潜力,但其临床适用性面临挑战。氧化还原生物标志物的半衰期通常较短,且在血液中的含量很少,这使得它们难以识别和测量。生物标志物数据的解释也可能受到混杂因素和各种氧化应激途径复杂相互作用的影响。因此,需要深入的验证研究以及开发灵敏且精确的检测方法来解决这些问题。在寻找氧化还原生物标志物的过程中,应用了质谱分析、免疫测定和分子诊断等前沿技术。新的平台和技术使得准确检测和监测氧化还原生物标志物成为可能,这有助于它们在临床环境中的应用。我们对RNS和ROS参与心血管疾病的认识不断扩展,使得开发氧化还原生物标志物作为诊断和预后工具成为可能。克服与其应用相关的挑战并利用先进的检测技术,这将提高它们的临床适用性,最终将有益于心血管疾病的管理和治疗。

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